Sorbent Materials
Sorbent materials used in solution-based separation processes usually offer adsorptive selectivity to retain the solutes of interest. Chemical, biochemical, radiochemical and pharmaceutical separations are mainly based on the use of any one or more of the following types of sorbent:                Ion-pair and ion-exchange sorbents that contain ionogenic/ion-exchange groups in a solid polymeric matrix;        Normal-phase solid phase extraction (SPE) sorbents including bare silica, alumina, FLORISIL® (synthetic magnesium silicate) and silica chemically modified with polar groups such as amino, cyano or diol groups; or        Reversed-phase SPE sorbents that contain alkyl chains bonded to a solid silica support; and/or        Mixed-mode SPE sorbents containing alkyl chains and ion exchange groups bonded to the same solid support.        
Metal oxide sorbents, including alumina, silica and ion-exchange sorbents, are particularly useful in radiochemical separations and radioisotope production and several different methods for the production of single and mixed metal oxides and hydrated oxides are known. Functionalised silica-based sorbents may also be utilised as reversed-phase, ion-exchange and mixed-mode SPE sorbents. However, many of these sorbent materials act as mono-functional sorbents, as they are based on a single active group present on the surface of the sorbent material. The application of such materials to separations is therefore limited, due to the limited adsorption selectivity and high adsorption competition of different solutes in the solution on the same active/functional group of the sorbent. This also reduces the dynamic adsorption capacity of the sorbent for the solute of interest, and as a result, adsorption competition of different solutes on the same single functional/active group of the sorbent may decrease the resolution of the separation process due to an overload of the sorbent. The solute selectivity of the monofunctional sorbents in a given separation medium is usually not tunable, which makes the separation process unmanageable.
Mixed metal oxides known in the art may exist as either (a) a homogeneous mixture of metal oxides (homogeneous distribution of molecules or of particles of functional metal oxides in the bulky mass of the sorbent) or (b) an inhomogeneous mixture of metal oxides (e.g., when the surfaces of metal oxide support particles are coated with single or mixed functional metal oxides and/or when the particles of functional metal oxide are embedded in the metal oxide matrix support). These sorbents have the disadvantage that the majority of the functional groups form a bulky inert particle mass via cross-linking (-M-O-M-)n.
Other sorbent materials known in the art are synthesised by coating mono-functional organic groups on the surface of silica, which may be produced by hydrolysis of silicon alkoxides in alkali solution or by hydrolysis of sodium silicate in acidic solutions. Silica sorbents synthesised using these methods commonly have a specific surface area of 300-600 m2/g, and have limited adsorption capacity due to the limited number of surface silanol groups available for covalent coupling with functional organic compounds. Efforts have been made to increase the specific surface area of such silicas and consequently to increase the number of accessible silanol groups. For example, surfactant/directing agent templated mesoporous silicas may have specific surface areas as high as 1000 m2/g or more. However, to remove the templating agent, dehydration and calcination steps are required and these additional steps can reduce the number of hydroxyl groups and increase the hydrophobic character of the silica. This may lead to difficulty in coupling functional organic compounds to the surface to produce a sorbent of high adsorption capacity. Efforts have thus also been made to remove the calcination step from such processes. However, a significant amount of surfactant residue is then found in the final silica product, reducing its utility as a sorbent material.
Radionuclide Production
Today, the technecium-99m radionuclide (99mTc) is used in approximately 85% of diagnostic imaging procedures in nuclear medicine worldwide. 99mTc is produced from the radioactive decay of its parent radioisotope molybdenum-99 (99Mo). Currently, global demand for 99Mo is primarily met through fission of uranium-235 irradiated in a nuclear reactor or through a neutron capture nuclear reaction using molybdenum-98. However, the 99Mo produced in the neutron capture method generally has a specific activity 10,000 times lower than that of fission-produced 99Mo.
Subsequent to manufacture, the 99Mo is then purified and supplied to manufacturers of 99Mo/99mTc generators around the world. 99mTc is then delivered to users in the form of these 99Mo/99mTc generators. Rhenium-188 (188Re) is also used in nuclear medicine procedures and therapies and is similarly derived from a tungsten-188/rhenium-188 (188W/188Re) generator.
A 99Mo/99mTc generator, colloquially known as a “technetium cow” or “moly cow”, is a device used to extract the metastable isotope of technetium (99mTc) from the radioactive decay of 99Mo. Molybdenum-99 has a half-life (t1/2) of approximately 66 hours. As such, it can be easily transported over long distances to radiopharmacies where its decay product, 99mTc (t1/2=6 hours), is extracted by normal saline elution. In such generators, 99Mo decays and produces 99mTc, which is eluted from the generator with a saline solution and results in a saline solution containing 99mTc as the pertechnetate ion, [99mTcO4]−, with sodium as the counterbalancing cation.
However, the low 99Mo adsorption capacity and/or poor adsorption-desorption kinetics of generator packing materials (e.g., alumina, polymeric zirconium and titanium compound sorbents, sulfated alumina, aluminium-sulfated zirconia, nanocrystalline zirconia, titania and alumina and ceramic sorbents of mixed zirconium and titanium oxides) is challenging the use of low specific activity 99Mo derived from neutron capture processes, in particular because a large column is required to produce a generator of acceptable activity, which in turn requires a large volume of the eluent to elute patient-dose quantities of 99mTc. Large eluent volumes then cause the radioactive concentration of the 99mTc-pertechnetate to become unacceptably low for use in most radiopharmaceutical diagnostic procedures. Hence, generator packing materials used in radiochemical separations in general, and particularly in medically useful 99mTc and 188Re radioisotope production, need further improvement. Additionally, there is a need for a further purification and/or concentration step to obtain daughter radionuclides from the generator eluates with suitable purity and concentration, e.g., for use in radiopharmaceutical diagnostic procedures.
Methods for said concentration of daughter radionuclides from radioisotope generator saline eluates have been used in clinical practice to obtain 99mTc and 188Re from 99Mo/99mTc and 188W/188Re generator systems, respectively. Such methods were initially developed for concentration of 188Re from 188W/188Re generators. In this system, the generator normal saline eluent is first passed through a small column of cation exchange resin in Ag form, which traps the chloride anion and allows subsequent in-tandem passage through a sorbent column such as QMA (quaternary methylammonium) anion trapping cartridge to specifically trap the target perrhenate ([ReO4]−) or pertechnetate ([TcO4]−) anions. The target anions are then removed with a small volume of normal saline ready for radiolabelling use and/or injection. Sorbents currently used for this purpose are alumina, zircona, ion-exchange resins Dowex®-1x8 and AG-1x8, DEAE (diethylaminoethyl)-cellulose sorbent, Accell QMA Sep-Pak® (a silica-based anion-exchange resin with surface functionality —C(O)NH(CH2)3N(CH3)3+Cl−), and BondElut® SAX (a silica-based anion-exchange resin with surface functionality —Si(CH3)2—(CH2)3N(CH3)3+Cl−). All of these sorbents are monofunctional, and the [99mTcO4]− and [188ReO4]− ions must compete with contaminant ions [99MoO4]2−, [188WO4]2−, and Cl−, which always accompany the [99mTcO4]− and [188ReO4]− ions in the solution, for adsorption sites on the sorbent material. This makes the purification/concentration process less effective. Further, the distribution coefficient (Kd) values of [99mTcO4]− and [188ReO4]− ions in physiological 0.9% NaCl solution is not able to be adjusted so as to facilitate the purification/concentration process.
The use of new sorbents in chemical and radiochemical purification, separation and concentration is needed to improve the performance of 99mTc and 188Re generators and to increase the 99mTc and/or 188Re concentration in the eluate. Hence, the present invention seeks to provide sorbent materials of high adsorption capacity for use with radioisotope generators and in radioisotope concentrator devices.
It is an object of the present invention to at least partially overcome or at least ameliorate one or more of the above outlined disadvantages of existing sorbent materials.